Subclassification of Koos grade 4 vestibular schwannoma: insights into tumor morphology for predicting postoperative facial nerve function.

OBJECTIVE: Koos grade 4 vestibular schwannoma (KG4VS) is a large tumor that causes brainstem displacement and is generally considered a candidate for surgery. Few studies have examined the relationship between morphological differences in KG4VS other than tumor size and postoperative facial nerve function. The authors have developed a landmark-based subclassification of KG4VS that provides insights into the morphology of this tumor and can predict the risk of facial nerve injury during microsurgery. The aims of this study were to morphologically verify the validity of this subclassification and to clarify the relationship of the position of the center of the vestibular schwannoma within the cerebellopontine angle (CPA) cistern on preoperative MR images to postoperative facial nerve function in patients who underwent microsurgical resection of a vestibular schwannoma. METHODS: In this paper, the authors classified KG4VSs into two subtypes according to the position of the center of the KG4VS within the CPA cistern relative to the perpendicular bisector of the porus acusticus internus, which was the landmark for the subclassification. KG4VSs with ventral centers to the landmark were classified as type 4V, and those with dorsal centers as type 4D. The clinical impact of this subclassification on short- and long-term postoperative facial nerve function was analyzed. RESULTS: In this study, the authors retrospectively reviewed patients with vestibular schwannoma who were treated surgically via a retrosigmoid approach between January 2010 and March 2020. Of the 107 patients with KG4VS who met the inclusion criteria, 45 (42.1%) were classified as having type 4V (KG4VSs with centers ventral to the perpendicular bisector of the porous acusticus internus) and 62 (57.9%) as having type 4D (those with centers dorsal to the perpendicular bisector). Ventral extension to the perpendicular bisector of the porus acusticus internus was significantly greater in the type 4V group than in the type 4D group (p < 0.001), although there was no significant difference in the maximal ventrodorsal diameter. The rate of preservation of favorable facial nerve function (House-Brackmann grades I and II) was significantly lower in the type 4V group than in the type 4D group in terms of both short-term (46.7% vs 85.5%, p < 0.001) and long-term (82.9% vs 96.7%, p = 0.001) outcomes. Type 4V had a significantly negative impact on short-term (OR 7.67, 95% CI 2.90-20.3; p < 0.001) and long-term (OR 6.05, 95% CI 1.04-35.0; p = 0.045) facial nerve function after surgery when age, tumor size, and presence of a fundal fluid cap were taken into account. CONCLUSIONS: The authors have delineated two different morphological subtypes of KG4VS. This subclassification could predict short- and long-term facial nerve function after microsurgical resection of KG4VS via the retrosigmoid approach. The risk of postoperative facial palsy when attempting total resection is greater for type 4V than for type 4D. This classification into types 4V and 4D could help to predict the risk of facial nerve injury and generate more individualized surgical strategies for KG4VSs with better facial nerve outcomes.

Delayed facial palsy after resection of vestibular schwannoma: does it influence long-term facial nerve functional outcomes?

OBJECTIVE: Delayed facial palsy (DFP) is a common and unique complication after resection of vestibular schwannoma (VS). Few studies have focused on the clinical question of whether patients with DFP can be expected to have the same long-term prognosis in terms of facial nerve function as those without DFP based on their facial nerve function immediately postoperatively. This study aimed to clarify the clinical impact of DFP on the long-term functional status of the facial nerve after VS resection. METHODS: The authors retrospectively reviewed patients with sporadic VS who were treated surgically via a retrosigmoid approach between January 2002 and March 2020. DFP was defined as de novo deterioration of facial nerve function by a House-Brackmann (HB) grade ≥ I more than 72 hours postoperatively. The incidence of DFP after VS resection and its impact on long-term facial nerve function were analyzed. RESULTS: DFP developed in 38 (14.3%) of 266 patients who met the inclusion criteria. The median latency until DFP onset postoperatively was 8.5 days. When facial nerve function was normal immediately postoperatively, the rate of preservation of favorable facial nerve function (HB grade I or II) at 24 months postoperatively was 100% for all patients regardless of whether they developed DFP. In contrast, when facial nerve dysfunction was present immediately postoperatively, the rate of preservation of favorable facial nerve function at 24 months postoperatively was significantly lower in patients with DFP than in those without DFP (77.8% vs 100% in patients with HB grade II immediately postoperatively, p = 0.001; 50.0% vs 90.3% in those with HB grade III immediately postoperatively, p = 0.042). DFP development had a significantly negative impact on the long-term functional status of the facial nerve postoperatively when age, tumor size, and HB grade immediately postoperatively were taken into account (OR 0.04, 95% CI 0.01-0.20; p < 0.001). CONCLUSIONS: DFP can be a minor complication when normal facial nerve function is observed immediately after surgery. However, when facial nerve dysfunction is present immediately after surgery, even if mild, the long-term prognosis for facial nerve function is significantly worse in patients with DFP than in those without DFP.

Effects of carotid revascularization on cognitive function and brain functional connectivity in carotid stenosis patients with cognitive impairment: a pilot study.

OBJECTIVE: Carotid stenosis can lead to both cognitive impairment (CI) and ischemic stroke. Although carotid revascularization surgery, which includes carotid endarterectomy (CEA) and carotid artery stenting (CAS), can prevent future strokes, its effect on cognitive function is controversial. In this study, the authors examined resting-state functional connectivity (FC) in carotid stenosis patients with CI undergoing revascularization surgery, with a particular focus on the default mode network (DMN). METHODS: Twenty-seven patients with carotid stenosis who were scheduled to undergo CEA or CAS between April 2016 and December 2020 were prospectively enrolled. A cognitive assessment, including the Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB), and Japanese version of the Montreal Cognitive Assessment (MoCA), as well as resting-state functional MRI, was performed 1 week preoperatively and 3 months postoperatively. For FC analysis, a seed was placed in the region associated with the DMN. The patients were divided into two groups according to the preoperative MoCA score: a normal cognition (NC) group (MoCA score ≥ 26) and a CI group (MoCA score < 26). The difference in cognitive function and FC between the NC and CI groups was investigated first, and then the change in cognitive function and FC after carotid revascularization was investigated in the CI group. RESULTS: There were 11 and 16 patients in the NC and CI groups, respectively. The FC of the medial prefrontal cortex with the precuneus and that of the left lateral parietal cortex (LLP) with the right cerebellum were significantly lower in the CI group than in the NC group. In the CI group, significant improvements were found in MMSE (25.3 vs 26.8, p = 0.02), FAB (14.4 vs 15.6, p = 0.01), and MoCA scores (20.1 vs 23.9, p = 0.0001) after revascularization surgery. Significantly increased FC of the LLP with the right intracalcarine cortex, right lingual gyrus, and precuneus was observed after carotid revascularization. In addition, there was a significant positive correlation between the increased FC of the LLP with the precuneus and improvement in the MoCA score after carotid revascularization. CONCLUSIONS: These findings suggest that carotid revascularization, including CEA and CAS, might improve cognitive function based on brain FC in the DMN in carotid stenosis patients with CI.

Endovascular Treatment of Borden Type III Transverse-sigmoid Sinus Dural Arteriovenous Fistulas: a Single-center 12-year Experience.

PURPOSE: The objective of this study was to evaluate our 12-year experience in treating Borden type III transverse-sigmoid sinus (TSS) dural arteriovenous fistulas (DAVFs) and discuss the technical aspects of ipsilateral and contralateral transvenous embolization (TVE) approaches. METHODS: We retrospectively reviewed charts of consecutive patients with TSS DAVF treated with multimodal treatment between April 2008 and March 2020. The baseline patient characteristics, imaging data, details of procedure, data sets of sinus pressure monitoring, and clinical results were systematically collected. RESULTS: Of 44 patients with TSS DAVF who were treated during study periods, 23 patients of Borden type III were extracted. Among the 23 patients, 18 with transfemoral TVE were included for analysis. TVE was performed using an ipsilateral approach in 8 patients and a contralateral approach in 10. Pressure monitoring data revealed that initial mean sinus pressure (43.5 mmHg vs. 29.5 mmHg; P = 0.033), maximum sinus pressure during the procedure (69.0 mmHg vs. 40.5 mmHg; P = 0.011), and sinus pressure gradient (22.5 mmHg vs. 5.5 mmHg; P = 0.021) were significantly higher in the ipsilateral approach group. The complete obliteration rate by primary embolization was 94% in our cohort with the recurrence rate of 5.6% with a median follow-up period of 57 months. CONCLUSION: Our study showed the durability of TVE for patients with Borden type III TSS DAVF. TVE performed via the contralateral approach might prevent a potentially dangerous increase in intraprocedural sinus pressure and cortical venous reflux.

Presence of a fundal fluid cap on preoperative magnetic resonance imaging may predict long-term facial nerve function after resection of vestibular schwannoma via the retrosigmoid approach.

OBJECTIVE: Preservation of neurological function is a priority when performing a resection of a vestibular schwannoma (VS). Few studies have examined the radiographic value of a fundal fluid cap-i.e., cerebrospinal fluid in the lateral end of a VS within the internal auditory canal-for prediction of postoperative neurological function. The aim of this study was to clarify whether the presence of a fundal fluid cap on preoperative magnetic resonance images has a clinical impact on facial nerve function after resection of VSs. METHODS: The presence of a fundal fluid cap and its prognostic impact on long-term postoperative facial nerve function were analyzed. RESULTS: A fundal fluid cap was present in 102 of 143 patients who underwent resection of sporadic VSs via the retrosigmoid approach. Facial nerve function was acceptable (House-Brackmann grade I-II) immediately after surgery in 82 (80.4%) patients with a fundal fluid cap and in 26 (63.4%) of those without this sign. The preservation rate of facial nerve function increased in a time-dependent manner after surgery in patients with a fundal fluid cap but plateaued by 3 months postoperatively in those without a fundal fluid cap; the difference was statistically significant at 12 months (96.1% vs 82.9%, p = 0.013) and 24 months (97.1% vs 82.9%, p = 0.006) after surgery. The presence of a fundal fluid cap had a significantly positive effect on long-term facial nerve function at 24 months after surgery when tumor size and intraoperative neuromonitoring response were taken into account (OR 5.55, 95% CI 1.12-27.5, p = 0.034). CONCLUSIONS: Neuromonitoring-guided microsurgery for total resection of VSs is more likely to be successful in terms of preservation of facial nerve function if a fundal fluid cap is present. This preoperative radiographic sign could be helpful when counseling patients and deciding the treatment strategy.

Stent implantation in a patient with non-hemorrhagic vertebral artery dissection associated with severe, continuously progressive stenosis in the posterior inferior cerebellar artery bifurcation region: A case report.

Generally, the prognosis of non-hemorrhagic vertebral artery dissection is good. Treatment should be considered when stenosis progresses or when an aneurysm is formed. However, no clear treatment policy has been established. The purpose of this case report was to describe the treatment policy for non-hemorrhagic onset vertebral artery dissection with severe stenosis around the posterior inferior cerebellar artery (PICA) bifurcation and aneurysm, where stent placement in the vertebral artery was difficult. This report describes healing without complications with stent implantation in the PICA performed to treat non-hemorrhagic vertebral artery dissection with associated severe, continuously progressive stenosis in the PICA bifurcation region. A 36-year-old woman was examined at the authors' hospital for persistent pain in the left posterior neck. Left vertebral arteriography revealed stenosis due to dissection around the PICA bifurcation and aneurysm formation at the distal position. Due to the progression of stenosis, there were concerns about PICA occlusion, and stent implantation in the vertebral artery was performed via the PICA. Neck pain ceased immediately after surgery, and 3 months later, cerebral angiography showed favorable patency of the PICA and decreased aneurysm size. This case suggests that stent implantation in the PICA might be a useful treatment option for non-hemorrhagic vertebral artery dissection with associated severe stenosis in the PICA bifurcation region.

The impact of hormonal dynamics and serum sodium fluctuations on symptomatic vasospasm after subarachnoid hemorrhage.

BACKGROUND: Symptomatic vasospasm (SVS) is a major cause of morbidity and mortality in aneurysmal subarachnoid hemorrhage (SAH), and serum sodium frequently decreases before SVS. Serum sodium changes might be regulated by sodium metabolism-related hormones. This multi-institutional prospective cohort study therefore investigated the measurement of sodium metabolism-related hormones to elucidate the pathophysiology of serum sodium changes in SAH. METHODS: SAH patients were treated with clipping or coiling from September 2017 to August 2020 at five hospitals. The laboratory data of 133 SAH patients were collected over 14 days and correlations between changes in serum sodium, sodium metabolism-related hormones (plasma adrenocorticotropic hormone (ACTH), serum cortisol, plasma arginine vasopressin (AVP)), and SVS were determined. Serum sodium concentrations were measured every day and serum sodium levels >135 mEq/L were maintained until day 14. RESULTS: Of the 133 patients, 18 developed SVS within 14 days of subarachnoid hemorrhage onset (SVS group) and 115 did not suffer from SVS (non-SVS group). Circulating AVP, ACTH, and cortisol concentrations were significantly higher on day 1 in the SVS group compared with the non-SVS group. Fluctuations in serum sodium in the SVS group were significantly higher than those in the non-SVS group. There were antiparallel fluctuations in serum sodium and potassium from days 2 to 14. CONCLUSIONS: Elevated levels of ACTH/cortisol and AVP on day 1 may be predictive markers for the occurrence of SVS. Multiple logistic regression analysis showed that serum sodium fluctuations were associated with SVS occurrence. Serum sodium fluctuations were associated with stress-related hormonal dynamics. (249 words).

Symptom-Based Opioid-Free Treatment for Persistent Postoperative Headache After Vestibular Schwannoma Resection via the Retrosigmoid Approach.

OBJECTIVE: Postoperative headache (POH) is a disturbing symptom following vestibular schwannoma (VS) resection. However, there are currently no treatment guidelines. The aim of this study was to evaluate the usefulness of symptom-based opioid-free treatments for persistent POH following VS resection. METHODS: Of 137 patients in whom sporadic VS was resected via the retrosigmoid approach, 74 had persistent POH beyond 3 postoperative months. Their symptoms were classified as tension-type headache, migraine, neuralgia, or other and were treated. We retrospectively analyzed the treatment outcomes during 2 postoperative years. RESULTS: Patients with persistent POH were significantly younger (P = 0.003) and had significantly smaller tumors (P = 0.001) and greater extent of resection (P = 0.04) than patients without POH. The most common simple symptom was tension-type headache in 56 patients, followed by migraine in 6 patients and neuralgia in 5 patients. All 7 patients with complex symptoms had a mixture of tension-type headache and migraine. Complete disappearance of POH was achieved in 40 (54%) patients, and a medication-free condition was achieved in 51 (69%). No patients had residual severe POH that could not be controlled with medication. Achievement of a medication-free outcome that included complete disappearance of persistent POH was significantly more common in patients with preserved facial nerve function (P = 0.008) and patients with simple symptoms (P < 0.001). CONCLUSIONS: A symptom-based approach is appropriate for understanding and managing persistent POH after VS resection with excellent pain control. Preserved facial nerve function and simple symptoms are significant prognostic factors for a medication-free outcome.

Glutamic Acid and Total Creatine as Predictive Markers for Epilepsy in Glioblastoma by Using Magnetic Resonance Spectroscopy Before Surgery.

OBJECTIVE: Epilepsy in glioblastoma patients significantly reduces their quality of life; however, little is known about the association between predicting epilepsy and metabolites in tumors. In this study, we used 3.0-T magnetic resonance imaging and 1H-magnetic resonance spectroscopy (MRS) to quantify metabolite concentrations in patients with varying epilepsy histories. METHODS: Fifty-one patients with glioblastoma underwent pretreatment 3.0-T MRI/1H-MRS scanning. Single-voxel (1.5 cm3) MRS, in an enhanced lesion, was acquired using a double-echo point-resolved spectroscopic sequence with chemical-shift selective water suppression. MRS data were quantified with linear combination model (LC-Model) software. We compared the MRS data between groups with and without epilepsy during the postoperative course (EP). RESULTS: The ratios of glutamate (Glu) and glutamate + glutamine (Glx) to total creatine (Glu/tCr and Glx/tCr) in the tumor were associated with epilepsy history. The receiver operating characteristic curve analysis showed that a Glu/tCr value of 1.81 was 70% sensitive and 90% specific for the prediction of EP (area under curve: 0.82). In the analysis excluding patients with preoperative epilepsy, a Glu/tCr value of 1.81 was 75% sensitive and 88% specific for the prediction (area under curve: 0.87). CONCLUSIONS: Intratumoral metabolite concentrations measured using pretreatment 3.0-T MRI/1H-MRS changed characteristically in the group with EP. Our study suggests that the Glu/tCr ratio in tumors has adequate reliability in predicting EP. Pretreatment MRS is a minimally invasive and simple procedure that can provide useful information on glioblastoma patients.

Potential of machine learning to predict early ischemic events after carotid endarterectomy or stenting: a comparison with surgeon predictions.

Carotid endarterectomy (CEA) and carotid artery stenting (CAS) are recommended for high stroke-risk patients with carotid artery stenosis to reduce ischemic events. However, we often face difficulty in determining the best treatment strategy. We aimed to develop an accurate post-CEA/CAS outcome prediction model using machine learning that will serve as a basis for a new decision support tool for patient-specific treatment planning. Retrospectively collected data from 165 consecutive patients with carotid stenosis underwent CEA or CAS and were divided into training and test samples. The following five machine learning algorithms were tuned, and their predictive performance was evaluated by comparison with surgeon predictions: an artificial neural network, logistic regression, support vector machine, random forest, and extreme gradient boosting (XGBoost). Seventeen clinical factors were introduced into the models. Outcome was defined as any ischemic stroke within 30 days after treatment including asymptomatic diffusion-weighted imaging abnormalities. The XGBoost model performed the best in the evaluation; its sensitivity, specificity, positive predictive value, and accuracy were 31.9%, 94.6%, 47.2%, and 86.2%, respectively. These statistical measures were comparable to those of surgeons. Internal carotid artery peak systolic velocity, low-density lipoprotein cholesterol, and procedure (CEA or CAS) were the most contributing factors according to the XGBoost algorithm. We were able to develop a post-procedural outcome prediction model comparable to surgeons in performance. The accurate outcome prediction model will make it possible to make a more appropriate patient-specific selection of CEA or CAS for the treatment of carotid artery stenosis.

Roles of skull base surgery and particle radiotherapy for orbital malignant tumors involving the skull base.

PURPOSE: To investigate the oncological outcomes of orbital malignant tumors invading the skull base. METHODS: A retrospective analysis was conducted on 16 patients with orbital malignant tumors invading the skull base. Eleven patients were treated with skull base surgery, four patients were treated with particle therapies, and one patient was treated with chemoradiotherapy (CRT) as initial treatment. RESULTS: The most frequent histological type was adenoid cystic carcinoma in seven patients, followed by squamous cell carcinoma in two patients. Local recurrence occurred in two of the six surgically treated patients who did not receive postoperative radiotherapy (RT) or CRT. One of them was successfully salvaged by RT, and the other died of disease. With a median follow-up of 24 months, the 2-year overall, local control, and disease-free survival rates of all patients were 82.5%, 87.5%, and 59%, respectively. CONCLUSIONS: Patients with positive surgical margins were at risk of local recurrence. Postoperative RT should be considered for all surgically treated patients.Level of Evidence: 4.

The Japan Neurosurgical Database: Statistics Update 2018 and 2019.

Each year, the Japan Neurosurgical Society (JNS) reports up-to-date statistics from the Japan Neurosurgical Database regarding case volume, patient demographics, and in-hospital outcomes of the overall cohort and neurosurgical subgroup according to the major classifications of main diagnosis. We hereby report patient demographics, in-hospital mortality, length of hospital stay, purpose of admission, number of medical management, direct surgery, endovascular treatment, and radiosurgery of the patients based on the major classifications and/or main diagnosis registered in 2018 and 2019 in the overall cohort (523283 and 571143 patients, respectively) and neurosurgical subgroup (177184 and 191595 patients, respectively). The patient demographics, disease severity, proportion of purpose of admission (e.g., operation, 33.9-33.5%) and emergent admission (68.4-67.8%), and in-hospital mortality (e.g., cerebrovascular diseases, 6.3-6.5%; brain tumor, 3.1-3%; and neurotrauma, 4.3%) in the overall cohort were comparable between 2018 and 2019. In total, 207783 and 225217 neurosurgical procedures were performed in the neurosurgical subgroup in 2018 and 2019, respectively, of which endovascular treatment comprised 19.1% and 20.3%, respectively. Neurosurgical management of chronic subdural hematoma (19.4-18.9%) and cerebral aneurysm (15.4-14.8%) was most common. Notably, the proportion of management of ischemic stroke/transient ischemic attack, including recombinant tissue plasminogen activator infusion and endovascular acute reperfusion therapy, increased from 7.5% in 2018 to 8.8% in 2019. The JNS statistical update represents a critical resource for the lay public, policy makers, media professionals, neurosurgeons, healthcare administrators, researchers, health advocates, and others seeking the best available data on neurosurgical practice.

Microvascular Decompression for Trigeminal Neuralgia: A Prospective, Multicenter Study.

BACKGROUND: Microvascular decompression (MVD) is the most effective procedure for the long-term management of trigeminal neuralgia (TGN). However, retrospective and single-center studies are inherently biased, and there are currently no prospective, multicenter studies. OBJECTIVE: To evaluate the short- and long-term outcomes and complications in patients with TGN who underwent MVD at specialized Japanese institutions. METHODS: We enrolled patients with TGN who underwent MVD between April 2012 and March 2015. We recorded their facial pain grade and complications at 7 d (short term), 1 yr (mid-term), and 3 yr (long term) postoperatively. RESULTS: There were 166 patients, comprising 60 men and 106 women (mean age 62.7 yr). Furthermore, 105 patients were aged over 60 yr. We conducted neuromonitoring in 84.3% of the cases. The complete pain relief, mortality, and complication rates at the short-term follow-up were 78.9%, 0%, and 16.3%, respectively. Overall, 155 patients (93.4%) completed the long-term follow-up, with the complete pain relief and complication rates of 80.0% and 5.2%, respectively. CONCLUSION: In the hands of experienced neurosurgeons, MVD for TGN can achieve high long-term curative effects. In addition, complications are uncommon and usually transient. Our results indicate that MVD is an effective and safe treatment for patients with TGN, including elderly patients.

Newly Identified Hemodynamic Parameter to Predict Thin-Walled Regions of Unruptured Cerebral Aneurysms Using Computational Fluid Dynamics Analysis.

BACKGROUND: The thin-walled regions (TIWRs) of intracranial aneurysms have a high risk of rupture during surgical manipulation. They have been reported to be predicted by wall shear stress and pressure (PS) based on computational fluid dynamics analysis, although this remains controversial. In this study, we investigated whether the oscillatory shear index (OSI) can predict TIWRs. METHODS: Twenty-five unruptured aneurysms were retrospectively analyzed; the position and orientation of the computational fluid dynamics color maps were adjusted to match the intraoperative micrographs. The red area on the aneurysm wall was defined as TIWR, and if most of the regions on the color map corresponding to TIWR were OSI low (lower quartile range), time-averaged wall shear stress (TAWSS) high, or PS high (upper quartile range), each region was defined as a matched region and divided by the total number of TIWRs to calculate the match rate. In addition, the mean values of OSI, TAWSS, and PS corresponding to TIWRs were quantitatively compared with those in adjacent thick-walled regions. RESULTS: Among 27 TIWRs of 25 aneurysms, 23, 10, and 14 regions had low OSI, high TAWSS, and high PS regions (match rate: 85.2%, 37.0%, and 51.9%), respectively. Receiver operating characteristic curve analysis demonstrated that OSI was the most effective hemodynamic parameter (area under the curve, 0.881), followed by TAWSS (0.798). Multivariate analysis showed that OSI was a significant independent predictor of TIWRs (odds ratio, 18.30 [95% CI, 3.2800-102.00], P < 0.001). CONCLUSIONS: OSI may be a unique predictor for TIWRs. Low OSI strongly corresponds with TIWRs of intracranial aneurysms.

Lactate Reprograms Energy and Lipid Metabolism in Glucose-Deprived Oxidative Glioma Stem Cells.

Fast-growing tumors satisfy their bioenergetic needs by supplementing glucose with alternative carbon sources. Cancer stem cells are the most versatile and robust cells within malignant tumors. They avoid potentially lethal metabolic and other types of stress through flexible reprogramming of relevant pathways, but it has remained unclear whether alternative carbon sources are important for the maintenance of their tumor-propagating ability. Here we assessed the ability of glycolytic and oxidative murine glioma stem cells (GSCs) to grow in an ultralow glucose medium. Sphere formation assays revealed that exogenous lactate and acetate reversed the growth impairment of oxidative GSCs in such medium. Extracellular flux analysis showed that lactate supported oxygen consumption in these cells, whereas metabolomics analysis revealed that it increased the intracellular levels of tricarboxylic acid cycle intermediates, ATP, and GTP as well as increased adenylate and guanylate charge. Lactate also reversed the depletion of choline apparent in the glucose-deprived cells as well as reprogrammed phospholipid and fatty acid biosynthesis. This metabolic reprogramming was associated with a more aggressive phenotype of intracranial tumors formed by lactate-treated GSCs. Our results thus suggest that lactate is an important alternative energetic and biosynthetic substrate for oxidative GSCs, and that it sustains their growth under conditions of glucose deprivation.

Geranylgeranylacetone attenuates cerebral ischemia-reperfusion injury in rats through the augmentation of HSP 27 phosphorylation: a preliminary study.

BACKGROUND: We previously reported that heat shock protein 27 (HSP27) phosphorylation plays an important role in the activation of glucose-6-phosphate dehydrogenase (G6PD), resulting in the upregulation of the pentose phosphate pathway and antioxidant effects against cerebral ischemia-reperfusion injury. The present study investigated the effect of geranylgeranylacetone, an inducer of HSP27, on ischemia-reperfusion injury in male rats as a preliminary study to see if further research of the effects of geranylgeranylacetone on the ischemic stroke was warranted. METHODS: In all experiments, male Wistar rats were used. First, we conducted pathway activity profiling based on a gas chromatography-mass spectrometry to identify ischemia-reperfusion-related metabolic pathways. Next, we investigated the effects of geranylgeranylacetone on the pentose phosphate pathway and ischemia-reperfusion injury by real-time polymerase chain reaction (RT-PCR), immunoblotting, and G6PD activity, protein carbonylation and infarct volume analysis. Geranylgeranylacetone or vehicle was injected intracerebroventricularly 3 h prior to middle cerebral artery occlusion or sham operation. RESULTS: Pathway activity profiling demonstrated that changes in the metabolic state depended on reperfusion time and that the pentose phosphate pathway and taurine-hypotaurine metabolism pathway were the most strongly related to reperfusion among 137 metabolic pathways. RT-PCR demonstrated that geranylgeranylacetone did not significantly affect the increase in HSP27 transcript levels after ischemia-reperfusion. Immunoblotting showed that geranylgeranylacetone did not significantly affect the elevation of HSP27 protein levels. However, geranylgeranylacetone significantly increase the elevation of phosphorylation of HSP27 after ischemia-reperfusion. In addition, geranylgeranylacetone significantly affected the increase in G6PD activity, and reduced the increase in protein carbonylation after ischemia-reperfusion. Accordingly, geranylgeranylacetone significantly reduced the infarct size (median 31.3% vs 19.9%, p = 0.0013). CONCLUSIONS: As a preliminary study, these findings suggest that geranylgeranylacetone may be a promising agent for the treatment of ischemic stroke and would be worthy of further study. Further studies are required to clearly delineate the mechanism of geranylgeranylacetone-induced HSP27 phosphorylation in antioxidant effects, which may guide the development of new approaches for minimizing the impact of cerebral ischemia-reperfusion injury.

Iatrogenic intracranial vessel dissection during mechanical thrombectomy rescued by emergent stenting: 2 case reports.

Intracranial vessel dissection is a procedural complication associated with endovascular treatment. However, there have been few reports on its potential causes and management during mechanical thrombectomy. In approximately 250 cases of mechanical thrombectomy over the past 5 years at our institution, iatrogenic intracranial dissection occurred in 2 patients (0.8%). In this report, we described these 2 cases that were rescued through emergent stenting. Mechanical thrombectomy, using both a stent retriever and an aspiration catheter, was performed for acute middle cerebral artery M2 occlusion in Patient 1 (a 69-year-old man) and for distal M1 occlusion in Patient 2 (an 83-year-old woman). In both cases, recanalization was achieved with the procedure, but irregular stenosis developed at the initially nonoccluded, but mildly arteriosclerotic, M1, after recanalization. During the thrombectomy procedure, the aspiration catheter sifted up to the arteriosclerotic M1. In both cases, the lesions were considered vessel dissection, due to a shift of the aspiration catheter tip into the arteriosclerotic vessel wall. Repeated percutaneous angiography with antithrombotic therapy failed to improve the lesions and to maintain the antegrade blood flow. Finally, lesions in each patient were successfully rescued through the use of emergent stenting. A drug-eluting stent for coronary use was deployed in Patient 1, and an Enterprise stent was applied in Patient 2. Inadvertent shift of the aspiration catheter into arteriosclerotic vessels can cause a serious intracranial vessel dissection. When performing mechanical thrombectomy, intracranial stents need to be available as rescue treatment devices to manage refractory iatrogenic intracranial vessel dissection.

Anatomical variation of the internal carotid artery and its implication to the endoscopic endonasal translacerum approach.

BACKGROUND: The endoscopic endonasal trans-lacerum approach (EETLA) is useful in handling skull base tumors around inferior petrous apex (IPA); however, its surgical corridor is exclusively a triangular space (supra-eustachian triangle [SET]), between the internal carotid artery (ICA) and eustachian tube. METHODS: We investigated correlation between SET size and extent of resection around the IPA (lateral extent of resection [EOR]) through a retrospective analysis of 15 surgeries using EETLA. RESULTS: Of 15 cases (9 chordomas, 4 chondrosarcomas, and 2 meningiomas), 20 sides of IPA were affected by the tumor. When being restricted to sides with severe lateral tumor extension beyond the midpoint of petrous ICA (10 sides), the SET size was significantly broader in the group with lateral EOR of ≥90% (p value = 0.019). CONCLUSIONS: The SET size was a powerful index of tumor resectability in EETLA, especially in cases with severe tumor extension. The individual anatomical variations should be considered when determining EETLA application.

Prospective, Multicenter Clinical Study of Microvascular Decompression for Hemifacial Spasm.

BACKGROUND: Microvascular decompression (MVD) is the most effective procedure for hemifacial spasm (HFS). MVD results from nonspecialized or low-volume institutes are not always reliable. Most studies on MVD for HFS are retrospective and single centered; to the best of our knowledge, no prospective, multicenter studies exist. OBJECTIVE: To evaluate short- and long-term outcomes and complications in patients who underwent MVD for HFS in specialized Japanese institutions, in this multicenter, prospective, cohort study. METHODS: Included patients had undergone MVD for HFS in study centers between April 2012 and March 2015. Patients' postoperative grade of involuntary movements and complications were recorded postoperatively at 7 d (short-term) and at 1 (mid-term) and 3 (long-term) yr. RESULTS: A total of 486 patients (150 men, 336 women; mean age 53.9 yr with 181 patients over 60 yr) were enrolled during the study period. Neuromonitoring was used in 96.3% of the cases. The complete cure rate of symptom relief, mortality rate, and complication rate at short-term follow-up were 70.6%, 0%, and 15%, respectively. The long-term follow-up was completed by 463 patients (95.3%); the complete cure rate of symptom relief and complication rate were 87.1% and 3.0%, respectively. CONCLUSION: Our study revealed that under expert guidance and intraoperative neuromonitoring, the long-term curative effect rate of MVD for HFS is high, while complications are uncommon and usually transient. Our results indicate that MVD is an effective and safe treatment for patients with HFS, including elderly patients.

Metabolic changes and anti-tumor effects of a ketogenic diet combined with anti-angiogenic therapy in a glioblastoma mouse model.

The ketogenic diet (KD) is a high fat and low carbohydrate diet that produces ketone bodies through imitation of starvation. The combination of KD and Bevacizumab (Bev), a VEGF inhibitor, is considered to further reduce the supply of glucose to the tumor. The metabolite changes in U87 glioblastoma mouse models treated with KD and/or Bev were examined using gas chromatography-mass spectrometry. The combination therapy of KD and Bev showed a decrease in the rate of tumor growth and an increase in the survival time of mice, although KD alone did not have survival benefit. In the metabolome analysis, the pattern of changes for most amino acids are similar between tumor and brain tissues, however, some amino acids such as aspartic acid and glutamic acid were different between tumors and brain tissues. The KD enhanced the anti-tumor efficacy of Bev in a glioblastoma intracranial implantation mouse model, based on lowest levels of microvascular density (CD31) and cellular proliferation markers (Ki-67 and CCND1) in KD + Bev tumors compared to the other groups. These results suggested that KD combined with Bev may be a useful treatment strategy for patients with GBM.